{
  "abstract": "DJ-1 is a redox-sensitive protein implicated in early-onset Parkinson's disease, and its mitochondrial localization protects against oxidative stress, but the mechanisms regulating its submitochondrial targeting and functional impact on mitochondrial integrity remain poorly understood. We identify voltage-dependent anion channel 1 (VDAC1) as a regulator of the submitochondrial distribution of DJ-1 during stress. Endogenous DJ-1 interacted with VDAC1, and loss of VDAC1 reduced stress-induced DJ-1 accumulation within the mitochondrial matrix. VDAC1-deficient neurons exhibited mitochondrial fragmentation, impaired oxidative phosphorylation, reduced ATP levels, altered reactive oxygen species (ROS) responses, and increased sensitivity to MPP+;. Matrix-targeted, but not outer-membrane-targeted, DJ-1 rescued basal, ATP-linked, and maximal respiration, improved mitochondrial morphology, and enhanced neuronal survival. ATP synthase inhibition also rapidly increased mitochondrial DJ-1, suggesting bioenergetic stress promotes its mitochondrial accumulation. Our findings identify compartment-specific localization as a key determinant of DJ-1 function and establish VDAC1-dependent matrix targeting as a critical mechanism supporting mitochondrial integrity during stress.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Clinical Neurosciences, Hotchkiss Brain Institute, Cumming School of Medicine, University of Calgary, Calgary, AB T2N 4N1, Canada"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 13,
  "authors": [
    {
      "name": "J. Taday"
    },
    {
      "name": "D. S. Im"
    },
    {
      "name": "S. J. Hewitt"
    },
    {
      "name": "G. Kaushik"
    },
    {
      "name": "S. M. Callaghan"
    },
    {
      "name": "U. Anilkumar"
    },
    {
      "name": "M. Brini"
    },
    {
      "name": "D. Figeys"
    },
    {
      "name": "Z. Khan"
    },
    {
      "name": "N. Khan"
    },
    {
      "name": "R. S. Slack"
    },
    {
      "name": "D. S. Park"
    },
    {
      "affs": [
        0
      ],
      "name": "A. Joselin"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/1eg90mdyj1zct.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.08.27.747597",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.08.27.747597v1.full",
  "id": "1eg90mdyj1zct",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.08.27.747597v1",
  "language": null,
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "biorxiv",
      "neuroscience"
    ],
    [
      "openalex",
      "2728|Parkinson's Disease Mechanisms and Treatments"
    ]
  ],
  "openalex": "W7204987336",
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.08.27.747597v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-08-27",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/1eg90mdyj1zct.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:18:27Z",
      "native_id": "10.64898/2026.08.27.747597",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.08.27.747597v1"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "biorxiv:neuroscience",
      "subfield": "neuroscience"
    }
  ],
  "title": "VDAC1 regulates stress-associated matrix localization of DJ-1 to support mitochondrial homeostasis and neuronal survival",
  "title_text": "VDAC1 regulates stress-associated matrix localization of DJ-1 to support mitochondrial homeostasis and neuronal survival",
  "type": "preprint",
  "updated_at": "2026-10-30T12:18:27Z",
  "url": "https://research.draconitic.com/paper/1eg90mdyj1zct",
  "venue": "bioRxiv",
  "versions": []
}